Lilly France SAS

In the phase 3 study, QWINT-1, efsitora was administered via four fixed doses once weekly in a single-use autoinjector in people with type 2 diabetes using basal insulin for the first time In a second phase 3 study, QWINT-3, efsitora also delivered non-inferior A1C reduction compared to daily insulin in people with type 2 diabetes switching from daily basal injections INDIANAPOLIS, Sept. 5, 2024 /PRNewswire/ -- Eli Lilly and Company (NYSE: LLY) today announced positive topline results from the QWINT-1 and QWINT-3 phase 3 clinical trials evaluating once weekly insulin efsitora alfa (efsitora) in adults with type 2 diabetes using basal insulin for the first time (insulin naïve) and in those who have switched from daily basal insulin injections, respectively. In these long-term treat-to-target trials, efsitora showed non-inferior A1C reduction compared to the most frequently used daily basal insulins globally. "Once weekly insulins, like efsitora, have the potential to transform diabetes care as we know it," said Jeff Emmick, M.D., Ph.D., senior vice president, product development, Lilly. "Many patients are reluctant to start insulin because of the burden it places on them. With a simple fixed-dose regimen, once-weekly efsitora could make it easier for people with diabetes to start and manage insulin therapy, while reducing the impact it has on their day-to-day lives." QWINT-1 evaluated the efficacy and safety of once weekly efsitora compared to once daily insulin glargine for 52 weeks. The trial randomized adults with type 2 diabetes who are insulin naïve to receive either efsitora once weekly in a single-use autoinjector or insulin glargine once daily. Efsitora was titrated across four fixed doses1 at four-week intervals, as needed for blood glucose control. The study's goal was to provide data supporting real-life applications of fixed dose regimens, which have the potential to make it easier for people living with diabetes to start and manage insulin therapy. The trial met its primary endpoint of non-inferior A1C reduction with efsitora compared to insulin glargine at week 52. For the efficacy estimand2,3, efsitora reduced A1C by 1.31% compared to 1.27% for insulin glargine, resulting in an A1C of 6.92% and 6.96%, respectively4. For the treatment-regimen estimand5,6, efsitora reduced A1C by 1.19% compared to 1.16% for insulin glargine, resulting in an A1C of 7.05% and 7.08%, respectively4. QWINT-3 evaluated the efficacy and safety of once weekly efsitora compared to once daily insulin degludec for 78 weeks in adults with type 2 diabetes currently treated with basal insulin. Participants were randomized 2:1 to receive either efsitora once weekly or insulin degludec once daily. The QWINT-3 trial met its primary endpoint of non-inferior A1C reduction with efsitora compared to insulin degludec at week 26. For the efficacy estimand7, efsitora reduced A1C by 0.86% compared to 0.75% for insulin degludec resulting in an A1C of 6.93% and 7.03%, respectively8. For the treatment-regimen estimand9, efsitora reduced A1C by 0.81% compared to 0.72% for insulin degludec resulting in an A1C of 6.99% and 7.08%, respectively10. Additionally, participants taking efsitora or insulin degludec spent approximately two hours more time in range (glucose 70-180 mg/dL) per day for weeks 22-26 compared to baseline. For the efficacy estimand11, participants taking efsitora spent 62.8% of time in range compared to 61.3% for insulin degludec for weeks 22-2612. For the treatment-regimen estimand13, participants taking efsitora spent 61.4% of time in range compared to 61% for insulin degludec14. Further, for the efficacy estimand, participants taking efsitora spent 38.3% of time in tight range (glucose 70-140 mg/dL) compared to 36.8% for insulin degludec for weeks 22-2615. In both QWINT-1 and QWINT-3, the overall safety and tolerability profile of efsitora was similar to that of daily basal insulin therapies for the treatment of type 2 diabetes. In QWINT-1, estimated combined rates of severe or clinically significant (blood glucose <54 mg/dL) hypoglycemic events per patient-year of exposure from weeks 0-52 were 0.50 with efsitora vs. 0.88 with insulin glargine – approximately 40% lower with efsitora than insulin glargine. In QWINT-3, estimated combined rates of severe or clinically significant (blood glucose <54 mg/dL) hypoglycemic events per patient-year of exposure from weeks 0-78 were 0.84 with efsitora vs. 0.74 with insulin degludec. Detailed results for QWINT-1 and QWINT-3 will be shared at an upcoming congress and published in a peer-reviewed journal. Additionally, detailed results for QWINT-2 and QWINT-5 will be presented at the European Association for the Study of Diabetes (EASD) Annual Meeting 2024. About the QWINT clinical trial program The QWINT phase 3 global clinical development program for insulin efsitora alfa (efsitora) in diabetes began in 2022 and has enrolled more than 4,000 people living with type 1 or type 2 diabetes across five global registration studies. QWINT-1 (NCT05662332) was a parallel-design, open-label, treat-to-target, randomized controlled clinical trial comparing the efficacy and safety of efsitora as a once weekly basal insulin using a fixed dose to insulin glargine for 52 weeks in insulin-naïve adults with type 2 diabetes. The trial randomized 796 participants across the U.S., Argentina, Mexico and Puerto Rico to receive efsitora once weekly or insulin glargine once daily administered subcutaneously. All participants treated with efsitora received a starting dose of 100 units followed by a fixed dose escalation to achieve a target fasting blood glucose of 80-130 mg/dL. Fasting blood glucose was measured every four weeks and participants escalated to fixed dosages of 150 units, 250 units and 400 units as appropriate. Participants with fasting blood glucose greater than 130 mg/dL on or after 16 weeks were transferred to flexible dosing. The primary objective of the trial was to demonstrate non-inferiority in reducing A1C at week 52 with efsitora compared to insulin glargine. QWINT-3 (NCT05275400) was a multicenter, randomized, parallel-design, open-label trial comparing the efficacy and safety of efsitora as a once-weekly basal insulin to insulin degludec for 78 weeks after a three-week lead-in period, and followed by a five-week safety follow up period, in adults with type 2 diabetes who are currently treated with basal insulin. The trial randomized 986 participants across the U.S., Argentina, Hungary, Japan, Korea, Poland, Puerto Rico, Slovakia, Spain and Taiwan to receive efsitora once weekly or insulin degludec once daily administered subcutaneously. The primary objective of the study was to demonstrate non-inferiority in reducing A1C at week 26 with efsitora compared to insulin degludec. About insulin efsitora alfa Insulin efsitora alfa (efsitora) is a once-weekly basal insulin, a fusion protein that combines a novel single-chain variant of insulin with a human IgG2 Fc domain. It is specifically designed for once-weekly subcutaneous administration, and with its low peak-to-trough ratio, it has the potential to provide more stable glucose levels (less glucose variability) throughout the week. Efsitora is in phase 3 development for adults with type 1 and 2 diabetes. About Lilly Lilly is a medicine company turning science into healing to make life better for people around the world. We've been pioneering life-changing discoveries for nearly 150 years, and today our medicines help more than 51 million people across the globe. Harnessing the power of biotechnology, chemistry and genetic medicine, our scientists are urgently advancing new discoveries to solve some of the world's most significant health challenges: redefining diabetes care; treating obesity and curtailing its most devastating long-term effects; advancing the fight against Alzheimer's disease; providing solutions to some of the most debilitating immune system disorders; and transforming the most difficult-to-treat cancers into manageable diseases. With each step toward a healthier world, we're motivated by one thing: making life better for millions more people. That includes delivering innovative clinical trials that reflect the diversity of our world and working to ensure our medicines are accessible and affordable. To learn more, visit Lilly.com and Lilly.com/news, or follow us on Facebook, Instagram and LinkedIn. P-LLY Cautionary Statement Regarding Forward-Looking Statements This press release contains forward-looking statements (as that term is defined in the Private Securities Litigation Reform Act of 1995), including statements about insulin efsitora alfa as a potential treatment for people with type 2 diabetes and the timeline for future readouts, presentations, and other milestones relating to insulin efsitora alfa and its clinical trials, and reflects Lilly's current beliefs and expectations. However, as with any pharmaceutical product, there are substantial risks and uncertainties in the process of drug research, development, and commercialization. Among other things, there is no guarantee that planned or ongoing studies will be completed as planned, that future study results will be consistent with study results to date, that insulin efsitora alfa will prove to be a safe and effective treatment for type 2 diabetes, that insulin efsitora alfa will receive regulatory approval, or that Lilly will execute its strategy as expected. For further discussion of these and other risks and uncertainties that could cause actual results to differ from Lilly's expectations, see Lilly's Form 10-K and Form 10-Q filings with the United States Securities and Exchange Commission. Except as required by law, Lilly undertakes no duty to update forward-looking statements to reflect events after the date of this release. 1 Participants treated with efsitora received a starting dose of 100 units of insulin, followed by escalation to fixed dosages of 150 units, 250 units and 400 units every 4 weeks, as needed, until achieving a target fasting blood glucose of 80-130 mg/dL. Participants with fasting blood glucose greater than 130 mg/dL on or after 16 weeks were transferred to flexible dosing. 2 The efficacy estimand represents the treatment effect had all participants adhered to the study drug without initiating rescue therapy for persistent severe hyperglycemia. 3 95% CI for treatment difference (-0.19% to 0.12%). 4 From a baseline A1C of 8.20% for efsitora and 8.28% for insulin glargine. 5 Treatment-regimen estimand represents the efficacy irrespective of adherence to the investigational medicine or introduction of rescue therapy for persistent severe hyperglycemia. 6 95% CI for treatment difference (-0.18% to 0.12%). 7 95% CI for treatment difference (-0.22% to 0%). 8 From a baseline A1C of 7.80% for efsitora and insulin degludec. 9 95% CI for treatment difference (-0.191% to 0.013%). 10 From a baseline A1C of 7.80% for efsitora and 7.79% for insulin degludec. 11 95% CI for treatment difference (-0.94 to 3.84). 12 From a baseline time in range of 51.95% for efsitora and 52.66% for insulin degludec. 13 95% CI for treatment difference (-1.88 to 2.72). 14 From a baseline time in range of 52.10% for efsitora and 52.43% for insulin degludec. 15 From a baseline tight time in range of 26.3% for efsitora and 27.1% for insulin degludec. SOURCE Eli Lilly and Company

176-week SURMOUNT-1 Phase 3 study in adults with pre-diabetes is the longest completed trial of tirzepatide to date Tirzepatide resulted in sustained weight loss through the treatment period, averaging a 22.9% decrease in body weight with the 15 mg dose at end of treatment Results are consistent with the combined pharmacology of GIP and GLP-1 receptor agonism INDIANAPOLIS, Aug. 20, 2024 /PRNewswire/ -- Eli Lilly and Company (NYSE: LLY) announced today positive topline results from the SURMOUNT-1 three-year study (176-week treatment period) evaluating the efficacy and safety of tirzepatide (Zepbound® and Mounjaro®) once weekly for long-term weight management and delay in progression to diabetes in adults with pre-diabetes and obesity or overweight. Weekly tirzepatide injections (5 mgi, 10 mg, 15 mg) significantly reduced the risk of progression to type 2 diabetes by 94% ii among adults with pre-diabetes and obesity or overweight compared to placebo. Additionally, treatment with tirzepatide resulted in sustained weight loss through the treatment period, with adults on the 15 mg dose experiencing a 22.9% ii average decrease in body weight compared to 2.1% for placebo in adults with pre-diabetes and obesity or overweight at the end of the treatment period. "Obesity is a chronic disease that puts nearly 900 million adults worldwide at an increased risk of other complications such as type 2 diabetes," said Jeff Emmick, M.D., Ph.D., senior vice president, product development, Lilly. "Tirzepatide reduced the risk of developing type 2 diabetes by 94% and resulted in sustained weight loss over the three-year treatment period. These data reinforce the potential clinical benefits of long-term therapy for people living with obesity and pre-diabetes." Tirzepatide was evaluated in 1,032 adults who had pre-diabetes at randomization and obesity or overweight for a treatment period of 176 weeks, followed by a 17-week off-treatment period (193 weeks in total). Results from the SURMOUNT-1 phase 3 study's primary analysis at 72 weeks in all participants were published in the New England Journal of Medicine in 2022. In a key secondary endpoint, tirzepatide led to a significant reduction in the risk of progression to type 2 diabetes in adults with pre-diabetes and obesity or overweight from baseline to week 176 (p<0.0001, controlled for type 1 error). For the efficacy estimandii, pooled doses of tirzepatide achieved significant results, demonstrating a 94% reduction in risk of progression to type 2 diabetes compared to placebo up to week 176. For the treatment-regimen estimandiii, pooled doses of tirzepatide resulted in a significant 93% reduction in risk of progression to type 2 diabetes compared to placebo up to week 176. In an additional key secondary endpoint, tirzepatide (10 mg and 15 mg) led to statistically significant weight reduction compared to placebo in adults with pre-diabetes and obesity or overweight from baseline to week 176 (p<0.001, controlled for type 1 error). For the efficacy estimandii, adults taking tirzepatide achieved average weight reductions of 15.4% (5 mgi), 19.9% (10 mg) and 22.9% (15 mg) compared to placebo (2.1%) at week 176. For the treatment-regimen estimandiii, adults taking tirzepatide achieved average weight reductions of 12.3% (5 mg i), 18.7% (10 mg) and 19.7% (15 mg) compared to placebo (1.3%) at week 176. During the 17-week off-treatment follow-up period, those who had discontinued from tirzepatide began to regain weight and had some increase in the progression to type 2 diabetes, resulting in an 88% reduction (p<0.0001, controlled for type 1 error) in the risk of progression to type 2 diabetes compared to placebo. The overall safety and tolerability profile of tirzepatide over the 193-week study was consistent with the previously published primary results at 72 weeks in SURMOUNT-1 and other tirzepatide clinical studies conducted for chronic weight management. The most frequently reported adverse events were typically gastrointestinal-related and generally mild to moderate in severity. The most common gastrointestinal-related adverse events for patients treated with tirzepatide were diarrhea, nausea, constipation and vomiting. Tirzepatide, a GIP and GLP-1 receptor agonist, works by activating the two hormone receptors. GLP-1 is a regulator of appetite and caloric intake. Nonclinical studies suggest the addition of GIP may further contribute to the regulation of food intake. Tirzepatide decreases calorie intake, and the effects are likely mediated by affecting appetite. In addition, tirzepatide stimulates insulin secretion in a glucose-dependent manner. Tirzepatide increases insulin sensitivity in patients with type 2 diabetes mellitus and these effects can lead to a reduction of blood glucose. These topline results provide evidence for reduced risk of progression to type 2 diabetes and long-term maintenance of weight loss with tirzepatide in adults with pre-diabetes and obesity or overweight. Detailed results will be submitted to a peer-reviewed journal and presented at ObesityWeek 2024, which will take place November 3-6. About SURMOUNT-1 SURMOUNT-1 (NCT04184622) was a multi-center, randomized, double-blind, parallel, placebo-controlled trial comparing the efficacy and safety of tirzepatide 5 mg, 10 mg and 15 mg to placebo as an adjunct to a reduced-calorie diet and increased physical activity in adults without type 2 diabetes who have obesity, or overweight with at least one of the following comorbidities: hypertension, dyslipidemia, obstructive sleep apnea (OSA) or cardiovascular disease. The 1,032 participants who had pre-diabetes at study commencement remained enrolled in SURMOUNT-1 for an additional 104 weeks of treatment following the initial 72-week completion date to evaluate the impact on body weight and potential differences in progression to type 2 diabetes at three years of treatment with tirzepatide compared to placebo. About tirzepatide Tirzepatide is a once-weekly GIP (glucose-dependent insulinotropic polypeptide) receptor and GLP-1 (glucagon-like peptide-1) receptor agonist. Tirzepatide is a single molecule that activates the body's receptors for GIP and GLP-1, which are natural incretin hormones. Both GIP and GLP-1 receptors are found in areas of the human brain important for appetite regulation. Tirzepatide has been shown to decrease food intake and modulate fat utilization. Studies of tirzepatide in chronic kidney disease (CKD) and in morbidity/mortality in obesity (MMO) are also ongoing. Lilly submitted data for tirzepatide in moderate-to-severe obstructive sleep apnea (OSA) and obesity to the U.S. Food and Drug Administration (FDA) and other global regulatory agencies earlier this year. Lilly plans to submit data for tirzepatide in heart failure with preserved ejection fraction (HFpEF) and obesity to the U.S. FDA and other global regulatory agencies later this year. Tirzepatide was approved by the U.S. FDA as Mounjaro® for adults with type 2 diabetes to improve glycemic control on May 13, 2022, and as Zepbound® for adults with obesity (a BMI of 30 kg/m2 or greater) or those who are overweight (a BMI of 27 kg/m2 or greater) who also have a weight-related comorbid condition on November 8, 2023. Tirzepatide is also commercialized as Mounjaro® in some global markets outside the U.S. for adults with obesity or those who are overweight who also have a weight-related comorbid condition. Tirzepatide is the only approved GIP (glucose-dependent insulinotropic polypeptide) and GLP-1 (glucagon-like peptide-1) treatment for chronic weight management. Both Mounjaro® and Zepbound® should be used as an adjunct to diet and exercise. INDICATION AND SAFETY SUMMARY WITH WARNINGS Zepbound® (ZEHP-bownd) is an injectable prescription medicine that may help adults with obesity, or with excess weight (overweight) who also have weight-related medical problems, lose weight and keep it off. It should be used with a reduced-calorie diet and increased physical activity. Zepbound contains tirzepatide and should not be used with other tirzepatide-containing products or any GLP-1 receptor agonist medicines. It is not known if Zepbound is safe and effective when taken with other prescription, over-the-counter, or herbal weight loss products. It is not known if Zepbound can be used in people who have had pancreatitis. It is not known if Zepbound is safe and effective for use in children under 18 years of age. Warnings - Zepbound may cause tumors in the thyroid, including thyroid cancer. Watch for possible symptoms, such as a lump or swelling in the neck, hoarseness, trouble swallowing, or shortness of breath. If you have any of these symptoms, tell your healthcare provider. Do not use Zepbound if you or any of your family have ever had a type of thyroid cancer called medullary thyroid carcinoma (MTC). Do not use Zepbound if you have Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). Do not use Zepbound if you have had a serious allergic reaction to tirzepatide or any of the ingredients in Zepbound. Zepbound may cause serious side effects, including: Severe stomach problems. Stomach problems, sometimes severe, have been reported in people who use Zepbound. Tell your healthcare provider if you have stomach problems that are severe or will not go away. Kidney problems (kidney failure). Diarrhea, nausea, and vomiting may cause a loss of fluids (dehydration), which may cause kidney problems. It is important for you to drink fluids to help reduce your chance of dehydration. Gallbladder problems. Gallbladder problems have happened in some people who use Zepbound. Tell your healthcare provider right away if you get symptoms of gallbladder problems, which may include pain in your upper stomach (abdomen), fever, yellowing of skin or eyes (jaundice), or clay-colored stools. Inflammation of the pancreas (pancreatitis). Stop using Zepbound and call your healthcare provider right away if you have severe pain in your stomach area (abdomen) that will not go away, with or without vomiting. You may feel the pain from your abdomen to your back. Serious allergic reactions. Stop using Zepbound and get medical help right away if you have any symptoms of a serious allergic reaction, including swelling of your face, lips, tongue or throat, problems breathing or swallowing, severe rash or itching, fainting or feeling dizzy, or very rapid heartbeat. Low blood sugar (hypoglycemia). Your risk for getting low blood sugar may be higher if you use Zepbound with medicines that can cause low blood sugar, such as a sulfonylurea or insulin. Signs and symptoms of low blood sugar may include dizziness or light-headedness, sweating, confusion or drowsiness, headache, blurred vision, slurred speech, shakiness, fast heartbeat, anxiety, irritability, mood changes, hunger, weakness or feeling jittery. Changes in vision in patients with type 2 diabetes. Tell your healthcare provider if you have changes in vision during treatment with Zepbound. Depression or thoughts of suicide. You should pay attention to changes in your mood, behaviors, feelings or thoughts. Call your healthcare provider right away if you have any mental changes that are new, worse, or worry you. Common side effects The most common side effects of Zepbound include nausea, diarrhea, vomiting, constipation, stomach (abdominal) pain, indigestion, injection site reactions, feeling tired, allergic reactions, belching, hair loss, and heartburn. These are not all the possible side effects of Zepbound. Talk to your healthcare provider about any side effect that bothers you or doesn't go away. Tell your healthcare provider if you have any side effects. You can report side effects at 1-800-FDA-1088 or . Before using Zepbound Your healthcare provider should show you how to use Zepbound before you use it for the first time. Tell your healthcare provider if you are taking medicines to treat diabetes including insulin or sulfonylureas which could increase your risk of low blood sugar. Talk to your healthcare provider about low blood sugar levels and how to manage them. If you take birth control pills by mouth, talk to your healthcare provider before you use Zepbound. Birth control pills may not work as well while using Zepbound. Your healthcare provider may recommend another type of birth control for 4 weeks after you start Zepbound and for 4 weeks after each increase in your dose of Zepbound. Review these questions with your healthcare provider: ❑ Do you have other medical conditions, including problems with your pancreas or kidneys, or severe problems with your stomach, such as slowed emptying of your stomach (gastroparesis) or problems digesting food? ❑ Do you take diabetes medicines, such as insulin or sulfonylureas? ❑ Do you have a history of diabetic retinopathy? ❑ Do you take any other prescription medicines or over-the-counter drugs, vitamins, or herbal supplements? ❑ Are you pregnant, plan to become pregnant, breastfeeding, or plan to breastfeed? Zepbound may harm your unborn baby. Tell your healthcare provider if you become pregnant while using Zepbound. It is not known if Zepbound passes into your breast milk. You should talk with your healthcare provider about the best way to feed your baby while using Zepbound. Pregnancy Exposure Registry: There will be a pregnancy exposure registry for women who have taken Zepbound during pregnancy. The purpose of this registry is to collect information about the health of you and your baby. Talk to your healthcare provider about how you can take part in this registry, or you may contact Lilly at 1-800-LillyRx (1-800-545-5979). How to take Read the Instructions for Use that come with Zepbound. Use Zepbound exactly as your healthcare provider says. Zepbound is injected under the skin (subcutaneously) of your stomach (abdomen), thigh, or upper arm. Use Zepbound 1 time each week, at any time of the day. Change (rotate) your injection site with each weekly injection. Do not use the same site for each injection. If you take too much Zepbound, call your healthcare provider, seek medical advice promptly, or contact a Poison Center expert right away at 1-800-222-1222. Learn more Zepbound is a prescription medicine. For more information, call 1-800-LillyRx (1-800-545-5979) or go to . This summary provides basic information about Zepbound but does not include all information known about this medicine. Read the information that comes with your prescription each time your prescription is filled. This information does not take the place of talking with your healthcare provider. Be sure to talk to your healthcare provider about Zepbound and how to take it. Your healthcare provider is the best person to help you decide if Zepbound is right for you. ZP CON CBS 08NOV2023 Zepbound® and its delivery device base are registered trademarks owned or licensed by Eli Lilly and Company, its subsidiaries, or affiliates. INDICATION AND SAFETY SUMMARY WITH WARNINGS Mounjaro® (mown-JAHR-OH) is an injectable medicine for adults with type 2 diabetes used along with diet and exercise to improve blood sugar (glucose). It is not known if Mounjaro can be used in people who have had inflammation of the pancreas (pancreatitis). Mounjaro is not for use in people with type 1 diabetes. It is not known if Mounjaro is safe and effective for use in children under 18 years of age. Warnings - Mounjaro may cause tumors in the thyroid, including thyroid cancer. Watch for possible symptoms, such as a lump or swelling in the neck, hoarseness, trouble swallowing, or shortness of breath. If you have any of these symptoms, tell your healthcare provider. Do not use Mounjaro if you or any of your family have ever had a type of thyroid cancer called medullary thyroid carcinoma (MTC). Do not use Mounjaro if you have Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). Do not use Mounjaro if you are allergic to it or any of the ingredients in Mounjaro. Mounjaro may cause serious side effects, including: Inflammation of the pancreas (pancreatitis). Stop using Mounjaro and call your healthcare provider right away if you have severe pain in your stomach area (abdomen) that will not go away, with or without vomiting. You may feel the pain from your abdomen to your back. Low blood sugar (hypoglycemia). Your risk for getting low blood sugar may be higher if you use Mounjaro with another medicine that can cause low blood sugar, such as a sulfonylurea or insulin. Signs and symptoms of low blood sugar may include dizziness or light-headedness, sweating, confusion or drowsiness, headache, blurred vision, slurred speech, shakiness, fast heartbeat, anxiety, irritability, or mood changes, hunger, weakness and feeling jittery. Serious allergic reactions. Stop using Mounjaro and get medical help right away if you have any symptoms of a serious allergic reaction, including swelling of your face, lips, tongue or throat, problems breathing or swallowing, severe rash or itching, fainting or feeling dizzy, and very rapid heartbeat. Kidney problems (kidney failure). In people who have kidney problems, diarrhea, nausea, and vomiting may cause a loss of fluids (dehydration), which may cause kidney problems to get worse. It is important for you to drink fluids to help reduce your chance of dehydration. Severe stomach problems. Stomach problems, sometimes severe, have been reported in people who use Mounjaro. Tell your healthcare provider if you have stomach problems that are severe or will not go away. Changes in vision. Tell your healthcare provider if you have changes in vision during treatment with Mounjaro. Gallbladder problems. Gallbladder problems have happened in some people who use Mounjaro. Tell your healthcare provider right away if you get symptoms of gallbladder problems, which may include pain in your upper stomach (abdomen), fever, yellowing of skin or eyes (jaundice), and clay-colored stools. Common side effects The most common side effects of Mounjaro include nausea, diarrhea, decreased appetite, vomiting, constipation, indigestion, and stomach (abdominal) pain. These are not all the possible side effects of Mounjaro. Talk to your healthcare provider about any side effect that bothers you or doesn't go away. Tell your healthcare provider if you have any side effects. You can report side effects at 1-800-FDA-1088 or . Before using Mounjaro Your healthcare provider should show you how to use Mounjaro before you use it for the first time. Talk to your healthcare provider about low blood sugar and how to manage it. If you take birth control pills by mouth, talk to your healthcare provider before you use Mounjaro. Birth control pills may not work as well while using Mounjaro. Your healthcare provider may recommend another type of birth control for 4 weeks after you start Mounjaro and for 4 weeks after each increase in your dose of Mounjaro. Review these questions with your healthcare provider: ❑ Do you have other medical conditions, including problems with your pancreas or kidneys, or severe problems with your stomach, such as slowed emptying of your stomach (gastroparesis) or problems digesting food? ❑ Do you take other diabetes medicines, such as insulin or sulfonylureas? ❑ Do you have a history of diabetic retinopathy? ❑ Are you pregnant, plan to become pregnant, breastfeeding, or plan to breastfeed? It is not known if Mounjaro will harm your unborn baby or pass into your breast milk. ❑ Do you take any other prescription medicines or over-the-counter drugs, vitamins, or herbal supplements? How to take Read the Instructions for Use that come with Mounjaro. Use Mounjaro exactly as your healthcare provider says. Mounjaro is injected under the skin (subcutaneously) of your stomach (abdomen), thigh, or upper arm. Use Mounjaro 1 time each week, at any time of the day. Do not mix insulin and Mounjaro together in the same injection. You may give an injection of Mounjaro and insulin in the same body area (such as your stomach area), but not right next to each other. Change (rotate) your injection site with each weekly injection. Do not use the same site for each injection. If you take too much Mounjaro, call your healthcare provider or seek medical advice promptly. Learn more Mounjaro is a prescription medicine. For more information, call 1-833-807-MJRO (833-807-6576) [or go to ]. This summary provides basic information about Mounjaro but does not include all information known about this medicine. Read the information that comes with your prescription each time your prescription is filled. This information does not take the place of talking with your healthcare provider. Be sure to talk to your healthcare provider about Mounjaro and how to take it. Your healthcare provider is the best person to help you decide if Mounjaro is right for you. TR CON CBS 14SEP2022 Mounjaro® and its delivery device base are registered trademarks owned or licensed by Eli Lilly and Company, its subsidiaries, or affiliates. About Lilly Lilly is a medicine company turning science into healing to make life better for people around the world. We've been pioneering life-changing discoveries for nearly 150 years, and today our medicines help more than 51 million people across the globe. Harnessing the power of biotechnology, chemistry and genetic medicine, our scientists are urgently advancing new discoveries to solve some of the world's most significant health challenges: redefining diabetes care; treating obesity and curtailing its most devastating long-term effects; advancing the fight against Alzheimer's disease; providing solutions to some of the most debilitating immune system disorders; and transforming the most difficult-to-treat cancers into manageable diseases. With each step toward a healthier world, we're motivated by one thing: making life better for millions more people. That includes delivering innovative clinical trials that reflect the diversity of our world and working to ensure our medicines are accessible and affordable. To learn more, visit Lilly.com and Lilly.com/news, or follow us on Facebook, Instagram and LinkedIn. P-LLY i Not controlled for type 1 error. ii The efficacy estimand represents efficacy had all patients remained on randomized treatment for the entire planned treatment duration (up to 176 weeks). iii The treatment-regimen estimand represents efficacy regardless of adherence to randomized treatment. Cautionary Statement Regarding Forward-Looking Statements This press release contains forward-looking statements (as that term is defined in the Private Securities Litigation Reform Act of 1995), including statements about tirzepatide injection for the treatment of adults with type 2 diabetes, tirzepatide as a potential long-term therapy for adults with pre-diabetes and obesity or overweight and the timeline for future presentations and other milestones relating to tirzepatide and its clinical trials, and reflects Lilly's current belief and expectations. However, as with any pharmaceutical product, there are substantial risks and uncertainties in the process of research development and commercialization. Among other things, there can be no guarantee that planned or ongoing studies will be completed as planned, that future study results will be consistent with the results to date, that tirzepatide will receive additional regulatory approvals, or that tirzepatide will be commercially successful. For further discussion of these and other risks and uncertainties, see Lilly's most recent Form 10-K and Form 10-Q filings with the United States Securities and Exchange Commission. Except as required by law, Lilly undertakes no duty to update forward-looking statements to reflect events after the date of this release. SOURCE Eli Lilly and Company

Broadens Lilly's immunology pipeline with Morphic's oral integrin therapies, including MORF-057 Reinforces the company's strategy of delivering potential first or best-in-class therapies in the field of gastroenterology INDIANAPOLIS, Aug. 16, 2024 /PRNewswire/ -- Eli Lilly and Company (NYSE: LLY) today announced the successful completion of its acquisition of Morphic Holding, Inc. (NASDAQ: MORF). Morphic is a biopharmaceutical company developing oral integrin therapies for treatment of serious chronic diseases, including a selective oral small molecule inhibitor of α4β7 integrin (known as MORF-057) for inflammatory bowel disease (IBD). "We are committed to exploring innovative approaches for immunologic diseases and believe Morphic's pipeline holds promise in improving outcomes and expanding treatment options for people with devastating conditions like IBD," said Daniel Skovronsky, M.D., Ph.D., chief scientific officer of Lilly and president, Lilly Research Laboratories and Lilly Immunology. "Acquiring Morphic reinforces our growing capabilities in gastroenterology, building on the strong foundation of Omvoh, our first-in-class molecule already approved and launched around the world for ulcerative colitis and under regulatory review for Crohn's disease. Further, the acquisition allows Lilly to research potential combination treatments that could better serve people beyond what is possible with currently available medicines." The Offer and the Merger Lilly's tender offer to acquire all of the issued and outstanding shares of common stock of Morphic (the "Shares"), at a purchase price of $57 per Share, net to the stockholder in cash, without interest thereon and subject to any applicable tax withholding, expired as scheduled at one minute past 11:59 p.m., Eastern time, on Aug. 15, 2024 and was not further extended. Computershare Trust Company, N.A., the depositary and paying agent for the tender offer, has advised Lilly that, as of the expiration of the tender offer, 46,731,511 Shares were validly tendered and not validly withdrawn, representing approximately 92.8% of the issued and outstanding Shares. Such Shares have been accepted for payment and will be promptly paid for in accordance with the terms of the tender offer. Following the completion of the tender offer, Lilly completed the acquisition of Morphic through the previously planned second-step merger. Morphic's common stock will be delisted from The Nasdaq Global Market. For Lilly, Citi is acting as the exclusive financial advisor and Kirkland & Ellis LLP is acting as legal counsel. For Morphic, Centerview Partners LLC is acting as the exclusive financial advisor. Evercore Group L.L.C. also provided advice to Morphic. Fenwick & West LLP is acting as legal counsel for Morphic. Indications and Usage for Omvoh™ (mirikizumab-mrkz) (in the United States) Omvoh™ is indicated for the treatment of moderately to severely active ulcerative colitis in adults. Important Safety Information for Omvoh (mirikizumab-mrkz) CONTRAINDICATIONS - Omvoh is contraindicated in patients with a history of serious hypersensitivity reaction to mirikizumab-mrkz or any of the excipients. WARNINGS AND PRECAUTIONS Hypersensitivity Reactions Serious hypersensitivity reactions, including anaphylaxis during intravenous infusion, have been reported with Omvoh administration. Infusion-related hypersensitivity reactions, including mucocutaneous erythema and pruritus, were reported during induction. If a severe hypersensitivity reaction occurs, discontinue Omvoh immediately and initiate appropriate treatment. Infections Omvoh may increase the risk of infection. Do not initiate treatment with Omvoh in patients with a clinically important active infection until the infection resolves or is adequately treated. In patients with a chronic infection or a history of recurrent infection, consider the risks and benefits prior to prescribing Omvoh. Instruct patients to seek medical advice if signs or symptoms of clinically important acute or chronic infection occur. If a serious infection develops or an infection is not responding to standard therapy, monitor the patient closely and do not administer Omvoh until the infection resolves. Tuberculosis Evaluate patients for tuberculosis (TB) infection prior to initiating treatment with Omvoh. Do not administer Omvoh to patients with active TB infection. Initiate treatment of latent TB prior to administering Omvoh. Consider anti-TB therapy prior to initiation of Omvoh in patients with a history of latent or active TB in whom an adequate course of treatment cannot be confirmed. Monitor patients for signs and symptoms of active TB during and after Omvoh treatment. In clinical trials, subjects were excluded if they had evidence of active TB, a history of active TB, or were diagnosed with latent TB at screening. Hepatotoxicity Drug-induced liver injury in conjunction with pruritus was reported in a clinical trial patient following a longer than recommended induction regimen. Omvoh was discontinued. Liver test abnormalities eventually returned to baseline. Evaluate liver enzymes and bilirubin at baseline and for at least 24 weeks of treatment. Monitor thereafter according to routine patient management. Consider other treatment options in patients with evidence of liver cirrhosis. Prompt investigation of the cause of liver enzyme elevation is recommended to identify potential cases of drug-induced liver injury. Interrupt treatment if drug-induced liver injury is suspected, until this diagnosis is excluded. Instruct patients to seek immediate medical attention if they experience symptoms suggestive of hepatic dysfunction. Immunizations Avoid use of live vaccines in patients treated with Omvoh. Medications that interact with the immune system may increase the risk of infection following administration of live vaccines. Prior to initiating therapy with Omvoh, complete all age-appropriate vaccinations according to current immunization guidelines. No data are available on the response to live or non-live vaccines in patients treated with Omvoh. ADVERSE REACTIONS Most common adverse reactions (≥2%) associated with Omvoh treatment are upper respiratory tract infections and arthralgia during induction, and upper respiratory tract infections, injection site reactions, arthralgia, rash, headache, and herpes viral infection during maintenance. MR HCP ISI UC APP Please click for Prescribing Information and Medication Guide for Omvoh. Please click for Instructions for Use included with the device. About Omvoh™ Omvoh (mirikizumab-mrkz) is an interleukin-23p19 antagonist indicated for the treatment of moderately to severely active ulcerative colitis in adults. Omvoh selectively targets the p19 subunit of IL-23 and inhibits the IL-23 pathway. Inflammation due to over-activation of the IL-23 pathway plays a critical role in the pathogenesis of ulcerative colitis. Treatment of ulcerative colitis with Omvoh starts with 300-mg IV infusions, once every four weeks for a total of three infusions, and transitions to two, 100-mg subcutaneous injections every four weeks during maintenance treatment. Omvoh™ and its delivery device base are trademarks owned by Eli Lilly and Company. About Lilly Lilly is a medicine company turning science into healing to make life better for people around the world. We've been pioneering life-changing discoveries for nearly 150 years, and today our medicines help more than 51 million people across the globe. Harnessing the power of biotechnology, chemistry and genetic medicine, our scientists are urgently advancing new discoveries to solve some of the world's most significant health challenges: redefining diabetes care; treating obesity and curtailing its most devastating long-term effects; advancing the fight against Alzheimer's disease; providing solutions to some of the most debilitating immune system disorders; and transforming the most difficult-to-treat cancers into manageable diseases. With each step toward a healthier world, we're motivated by one thing: making life better for millions more people. That includes delivering innovative clinical trials that reflect the diversity of our world and working to ensure our medicines are accessible and affordable. To learn more, visit Lilly.com and Lilly.com/news, or follow us on Facebook, Instagram and LinkedIn. C-LLY Cautionary Statement Regarding Forward-Looking Statements This press release contains forward-looking statements regarding Lilly's acquisition of Morphic, including the anticipated benefits and financial impact of the acquisition, Morphic's product candidates, including with respect to potential combination treatments involving Lilly's existing and future therapies, the delisting of Morphic's common stock, and ongoing and planned research and development. All statements other than statements of historical fact are statements that could be deemed forward-looking statements. Forward-looking statements reflect current beliefs and expectations; however, these statements involve inherent risks and uncertainties, including with respect to drug research, development and commercialization, Lilly's evaluation of the accounting treatment of the acquisition and its potential impact on its financial results and financial guidance, risks that the acquisition disrupts current plans and operations or adversely affects employee retention and any legal proceedings that may be instituted related to the acquisition. Actual results could differ materially due to various factors, risks and uncertainties. Among other things, there can be no guarantee that Lilly will realize the expected benefits of the acquisition, that product candidates will be approved on anticipated timelines or at all, that any products, if approved, will be commercially successful, that Lilly's financial results will be consistent with its expected 2024 guidance or that Lilly can reliably predict the impact of the acquisition on its financial results or financial guidance. For further discussion of these and other risks and uncertainties, see Lilly's most recent Form 10-K and Form 10-Q filings with the United States Securities and Exchange Commission. Except as required by law, Lilly undertakes no duty to update forward-looking statements to reflect events after the date of this press release. SOURCE Eli Lilly and Company